A Prospective Questionnaire-Based Study Evaluating Genetic Literacy and Impact of Brief Educational Intervention Among Breast Cancer Patients in a Low- to Middle-Income Country.

INTRODUCTION: A significant proportion of breast cancer cases are hereditary and are potentially preventable. However, adoption of the preventive measures remains a significant challenge, particularly because of to lack of knowledge and awareness in low- to middle-income countries. METHODS: This prospective study conducted at a high-volume tertiary care cancer center in North India to assess the knowledge, awareness, and attitudes of female breast cancer patients and impact of a brief educational intervention. The study involved three phases: pre-interventional assessment, educational intervention, and post-interventional assessment utilizing a structured questionnaire. RESULTS: The study involved 300 newly diagnosed breast cancer patients; 16.7% were familial. At the outset, 87.0% patients had low knowledge of risk factors, 90.3% about screening, and 32.7% about treatment. Awareness levels were low: 13.7% aware of familial risk and 2.7% of breast cancer genes. Affordability of genetic testing was low (15.2%), and interest in testing for self and family members was limited (32.0% and 26.3%). Following educational intervention, a significant positive percentage change was noticed in knowledge (risk factors: 12.8%, screening: 36.2%, treatment: 82%), awareness (familial risk: 66.7%, BRCA gene: 12.3%), and attitude (testing for self: 17.8%, family: 19.5%). CONCLUSIONS: This study highlights the significant knowledge gaps among breast cancer patients regarding genetics. The educational intervention led to notable improvements in knowledge, awareness, and attitudes, underscoring the importance of tailored patient education in breast cancer care.

Canonical WNT/ß-catenin signaling upregulates aerobic glycolysis in diverse cancer types.

Despite many efforts, a comprehensive understanding and clarification of the intricate connections within cancer cell metabolism remain elusive. This might pertain to intracellular dynamics and the complex interplay between cancer cells, and cells with the tumor stroma. Almost a century ago, Otto Warburg found that cancer cells exhibit a glycolytic phenotype, which continues to be a subject of thorough investigation. Past and ongoing investigations have demonstrated intricate mechanisms by which tumors modulate their functionality by utilizing extracellular glucose as a substrate, thereby sustaining the essential proliferation of cancer cells. This concept of "aerobic glycolysis," where cancer cells (even in the presence of enough oxygen) metabolize glucose to produce lactate plays a critical role in cancer progression and is regulated by various signaling pathways. Recent research has revealed that the canonical wingless-related integrated site (WNT) pathway promotes aerobic glycolysis, directly and indirectly, thereby influencing cancer development and progression. The present review seeks to gather knowledge about how the WNT/ß-catenin pathway influences aerobic glycolysis, referring to relevant studies in different types of cancer. Furthermore, we propose the concept of impeding the glycolytic phenotype of tumors by employing specific inhibitors that target WNT/ß-catenin signaling.

Fruit Quality Assessment of Novel Hybrid Pummelo × Sweet Orange and Its Molecular Characterization Using Acidity Specific Markers.

Research background: There is considerable diversity in newly developed pummelo × sweet orange citrus hybrids. Most hybrids showed lower peel thickness and high juice yield but there is a lack of information on fruit quality parameters and molecular characterization. Therefore, the aim of the current study is to determine the content of antioxidants and properties of the fresh juice of 24 new pummelo × sweet orange citrus hybrids (Citrus maxima [Burm. f.] Osbeck × Citrus sinensis [L.] Osbeck) and the parental genotypes along with molecular characteristics determined using acidity specific markers. Experimental approach: The correlation and estimate of inheritance of the fruit juice properties: ascorbic acid, total phenol, total flavonoid, total antioxidant, total soluble solid and sugar contents, pH, titratable acidity, along with sensory evaluation was performed. Molecular characterization of these hybrids was carried out using de novo generated acidity specific simple sequence repeat (SSR) markers. Results and conclusions: The main constituents of the fruit juice of pummelo × sweet orange hybrids were observed in the range of w(ascorbic acid)=40.00-58.13 mg/100 g, total phenols expressed as gallic acid equivalents w(GAE)=40.67-107.33 mg/100 g, total antioxidants expressed as Trolox equivalents b(Trolox)=2.03-5.49 µmol/g, total flavonoids expressed as quercetin equivalents w(QE)=23.67-59.33 mg/100 g, along with other properties: total soluble solids=7.33-11.33 %, w(total sugar)=2.10-5.76 %, w(reducing sugar)=1.69-2.78 %, w(non-reducing sugar)=0.39-3.17 % and titratable acidity 1.00-2.11 %. The above parameters differed significantly in the fruit juice of the evaluated pummelo × sweet orange hybrids. Considering these parameters, the hybrids SCSH 17-9, SCSH 13-13, SCSH 11-15 and SCSH 3-15 had superior antioxidant properties in terms of these parameters. A higher heritability (≥80 %) was also observed for all juice properties. Molecular characterization of pummelo × sweet orange hybrids showed that >50 % of the hybrids were grouped with medium acidity parents. Both molecular and biochemical parameter-based clustering showed that interspecific hybrids exhibit transgressive segregation with increased antioxidants that help alleviate the health problems. Novelty and scientific contribution: These newly developed pummelo × sweet orange citrus hybrids are a valuable source of high-quality antioxidants for a healthy diet. The identification of trait markers that enable selection at the seedling stage is of great benefit to citrus breeders, as the characteristic features of a mature tree are not yet visible at the juvenile stage.

Combination of 3PO analog PFK15 and siPFKL efficiently suppresses the migration, colony formation ability, and PFK-1 activity of triple-negative breast cancers by reducing the glycolysis.

Among all the subtypes of breast cancer, triple-negative breast cancer (TNBC) has been associated with the worst prognosis. Recently, for many solid tumors (including breast cancer) metabolic reprogramming has appeared as a cancer cell hallmark, and the elevated glycolytic pathway has been linked to their aggressive phenotype. In the present study, we evaluated the prognostic and therapeutic relevance of PFKFB3 (6-phosphofructo-2- kinase/fructose-2,6-bisphosphatase) in TNBCs. Prognostic significance of PFKFB3 expression was evaluated in overall breast cancers as well as in TNBCs. PFKFB3 inhibitor (3PO potent analogue i.e., PFK15) cytotoxicity in TNBC cell lines (MDA-MB-231 and MDA-MB-468) was analyzed using an MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Cancer cell physiological characteristics like clonogenicity and migration were also investigated after PFK15 treatment. As fructose-2,6-bisphosphate (F-2,6-BP), has been associated with increased PFK-1 activity, the effect of PFKFB3 inhibition by PFK15 was investigated on two major isoforms of phosphofructokinase-1 (PFK-1) in breast cancer, that is, phosphofructokinase-platelet type (PFKP) and phosphofructokinase-liver type (PFKL) (relevant to breast cancer). For PFKL inhibition, the siRNA approach was used. PFKFB3 expression was significantly correlated with inferior overall survival in breast cancer patients including TNBCs. PFK15 treatment in TNBC cells (i.e., MDA-MB-231 and MDA-MB-468) resulted in a decreased PFKP expression, thereby leading to reduced colony formation ability, migration rate, and extracellular lactate levels. However, to our surprise PFK15 treatment in both TNBC cells also resulted in elevated PFKL levels. Our results demonstrated that the combinatorial inhibition of PFK15 with siPFKL was more effective in TNBC cells, as it led to a decrease in colony formation ability, migration rate, extracellular lactate levels, and PFK-1 activity when compared with individual treatments. Using bona fide PFKFB3 inhibitor, that is, AZ67, we further show that AZ67 treatment to TNBC cells has no effect either on the expression of PFKP and PFKL, or on the lactate production. In summary, our present in vitro study demonstrated that 3PO derived PFK15 mechanism of action is totally different from AZ67 in TNBC cells. However, we advocate that the PFK15-mediated inhibition (along with PFKL) on the TNBCs migration, colony formation, and PFK-1 activity can be further explored for the therapeutic advantage of TNBC patients.

Whole exome sequencing identifies novel variants of PIK3CA and validation of hotspot mutation by droplet digital PCR in breast cancer among Indian population.

BACKGROUND: Breast cancer (BC) is the most common malignancy with very high incidence and relatively high mortality in women. The PIK3CA gene plays a pivotal role in the pathogenicity of breast cancer. Despite this, the mutational status of all exons except exons 9 and 20 still remains unknown. METHODS: This study uses the whole exome sequencing (WES) based approach to identify somatic PIK3CA mutations in Indian BC cohorts. The resultant hotspot mutations were validated by droplet digital PCR (ddPCR). Further, molecular dynamics (MD) simulation was applied to elucidate the conformational and functional effects of hotspot position on PIK3CA protein. RESULTS: In our cohort, PIK3CA showed a 44.4% somatic mutation rate and was among the top mutated genes. The mutations of PIK3CA were confined in Exons 5, 9, 11, 18, and 20, whereas the maximum number of mutations lies within exons 9 and 20. A total of 9 variants were found in our study, of which 2 were novel mutations observed on exons 9 (p.H554L) and 11 (p.S629P). However, H1047R was the hotspot mutation at exon 20 (20%). In tumor tissues, there was a considerable difference between copy number of wild-type and H1047R mutant was detected by ddPCR. Significant structural and conformational changes were observed during MD simulation, induced due to point mutation at H1047R/L position. CONCLUSIONS: The current study provides a comprehensive view of novel as well as reported single nucleotide variants (SNVs) in PIK3CA gene associated with Indian breast cancer cases. The mutation status of H1047R/L could serve as a prognostic value in terms of selecting targeted therapy in BC.

Evaluation of Dual Dye Technique for Sentinel Lymph Node Biopsy in Breast Cancer: Two-Arm Open-Label Parallel Design Non-Inferiority Randomized Controlled Trial.

INTRODUCTION: Radioisotope and blue dye are standard agents for performing sentinel lymph node (SLN) biopsy in breast cancer. The paucity of nuclear medicine facility poses logistic challenge. This study evaluated performance of radioisotope & methylene blue (MB) with indocyanine green (ICG) and MB for SLNB. PATIENTS AND METHODS: This randomized controlled trial was conducted from December 2019 to July 2022 comparing SLN identification proportions of radioisotope-blue dye [Group A] with dual dye (MB + ICG; Group B]. Secondary objective included time required and cost effectiveness of performing SLNB. Sample size of 70 (35 in each arm) was calculated. Upfront operable node negative early breast cancer was included in the study. Clinico-demographic data, number & type of SLN, time taken were noted. Cost analysis was done including the equipment, manpower & consumables. Chi-square/Fisher exact test was used to compare proportion between two groups. p value of less than 0.05 was considered to represent statistical significance. RESULTS: Seventy patients randomized to either group were similar in clinico-demographic and tumor characteristics. SLN identification rate (IR) was 91.43% in group A and 100% in group B. Overall IR of MB, radioisotope and ICG were 91.43%, 91.43% and 100%, respectively. Mean number of SLNs identified were 3 in group A and 4 in group B. Median time required for SLNB was 12 min and 14 min in either group, respectively. Cost of performing SLNB was higher in Group B. CONCLUSION: SLNB using dual dye is non-inferior to radioisotope-blue dye in upfront operable early breast cancer. Trial registration number Clinical Trial registry India CTRI/2020/02/023503.

Cytomorphology of paediatric hepatocellular carcinoma: A useful diagnostic adjunct.

INTRODUCTION: Hepatocellular carcinoma (HCC) is a common primary malignancy of the liver but is rare in the paediatric age group; thus, it may be misdiagnosed as the more common tumour, hepatoblastoma. Management varies in both these tumours, and pathological diagnosis thus plays an important role for definitive therapy. Only a few case reports available in the literature have described the cytological characteristics of paediatric HCC. The present study was thus planned to evaluate the cytomorphological features of paediatric HCC. METHODS: Cases diagnosed with HCC on ultrasound-guided fine needle aspiration cytology over a period of 14 years were retrieved. The cases were evaluated for detailed cytological features including cellularity, architecture, sinusoidal wrapping, trabecular thickness, necrosis, anisonucleosis, chromatin, nucleoli, nuclear contours, bi- or multinucleation, intranuclear and intracytoplasmic inclusions, naked nuclei, extra-medullary haematopoiesis, monomorphism, and nuclear overlapping. RESULTS: Twelve cases of HCC were included in the study. The median age at diagnosis was 10 years. Serum alpha-fetoprotein level was raised in most of them. Five of the 12 cases were characterised as moderately differentiated, three as poorly differentiated, two as well differentiated, and two as the fibrolamellar type of HCC. Cytohistological correlation was performed in seven cases. CONCLUSIONS: Ultrasound-guided fine needle aspiration serves as a useful tool to diagnose paediatric HCC and differentiate it from other primary hepatic malignancies, especially hepatoblastoma which closely mimics HCC in this age group, as serum alpha protein levels and imaging findings are unable to distinguish these two tumours.

Evaluation of cervical cancer screening during pregnancy in India: Human papillomavirus testing can change the paradigm.

Background The World Health Organization's call for elimination of cervical cancer envisages 70% screening coverage of women aged 35 and 45 years by an effective test. In India, this target seems unrealistic as awareness and access to cancer prevention services are poor. However, the institutional delivery rate is now >80%. We evaluated the acceptability and feasibility of human papillomavirus (HPV) testing and its role in screening during pregnancy. Methods This observational study recruited 275 pregnant women aged >25 years between 12 and 34 weeks of gestation for screening by cytology and HPV testing. Colposcopy was advised if either test was positive. Acceptability and feasibility were assessed by a questionnaire. Results Cytology and HPV reports were available for 269 subjects. The median age was 28 years and median parity was two. Only 98 (36.4%) had heard about carcinoma cervix. Awareness improved with education (p < 0.001). On cytology, only 4 (1.5%) were abnormal (atypical squamous cells of undetermined significance 3; low-grade squamous intraepithelial lesion 1). The prevalence of high-risk HPV infection was 8.2% (22/269). On colposcopy, all had the Swede score <5. No high-grade cervical intraepithelial neoplasia or carcinoma was detected. Pre-procedure, 183 (68.0%) subjects expressed apprehension, post-procedure 114 (42.4%) of them had realized that their apprehensions were unfounded. Women found screening to be more uncomfortable after 28 weeks of gestation (n=26/68; 38.2%; p<0.001). Physicians found the cervix more difficult to visualize after 20 weeks of gestation (p<0.001). Conclusions HPV screening at 16-20 weeks of pregnancy is acceptable, feasible, and can greatly improve screening coverage in resource-limited settings. Pregnancy is a good opportunity to improve awareness of the screening programmes.

Primary leiomyosarcoma of the vulva - a rare occurrence.

Vulval tumours are rare, representing merely 4% of all gynaecological neoplasms. 98% of vulvar lesions are benign, and only 2% are malignant. Of all vulvar malignancies, while squamous cell carcinoma is the most common malignancy, leiomyosarcomas of the vulva are extremely rare. Usually these tumours have nonspecific clinical manifestations, often leading to misdiagnoses of Bartholin cysts or abscesses. We describe a case of a 47-year-old woman who presented with a nonspecific painless swelling in the left vulva for 2 months which was diagnosed as leiomyosarcoma of the vulva on biopsy as well as resection.

Unveiling the Significance of FGF8 Overexpression in Orchestrating the Progression of Ovarian Cancer.

The asymptomatic nature, high rate of disease recurrence, and resistance to platinum-based chemotherapy highlight the need to identify and characterize novel target molecules for ovarian cancer. Fibroblast growth factor 8 (FGF8) aids in the development and metastasis of ovarian cancer; however, its definite role is not clear. We employed ELISA and IHC to examine the expression of FGF8 in the saliva and tissue samples of epithelial ovarian cancer (EOC) patients and controls. Furthermore, various cell assays were conducted to determine how FGF8 silencing influences ovarian cancer cell survival, adhesion, migration, and invasion to learn more about the functions of FGF8. In saliva samples, from controls through low-grade to high-grade EOC, a stepped overexpression of FGF8 was observed. Similar expression trends were seen in tissue samples, both at protein and mRNA levels. FGF8 gene silencing in SKOV3 cells adversely affected various cell properties essential for cancer cell survival and metastasis. A substantial reduction was observed in the cell survival, cell adhesion to the extracellular matrix, migration, and adhesion properties of SKOV3 cells, suggesting that FGF8 plays a crucial role in the development of EOC. Conclusively, this study suggests a pro-metastatic function of FGF8 in EOC.

Transvaginal Shear Wave Elastography for Assessment of Endometrial and Subendometrial Pathologies: A Prospective Pilot Study.

OBJECTIVE: To assess the role of shear wave elastography (SWE) in characterizing different endometrial and subendometrial pathologies. METHODS: Seventy-three women with pathologically proven endometrial and subendometrial pathologies were enrolled in this prospective study and assessed with transvaginal SWE. The elasticity values (in kiloPascals), and the ratio of mean elasticity of the endometrial lesion to myometrial elasticity (E/M ratio) were compared in different pathologies. RESULTS: There was a statistically significant difference (P <.001) in the mean, minimum, and maximum elasticity of the pathologies as well as the E/M ratio (P <.00001). In the analysis of the subgroups, the mean elasticity of endometrial polyp was statistically significantly lower than other subgroups (P <.01), while submucosal leiomyoma and focal adenomyoma had significantly higher values than other subgroups (P <.01). No statistically significant difference was noted in the mean elasticity of carcinoma and hyperplasia (P-.19). CONCLUSION: SWE is a potential adjunct to ultrasound that provides an additional paradigm to characterize endometrial and subendometrial masses.

Differential expression of miRNA in histological subtype of Wilms tumor.

INTRODUCTION: Wilms tumor is the most common renal malignancy in children and difficult to differentiate from other paediatric abdominal tumors radiologically, necessitating an invasive procedure for diagnosis. Previous studies have shown the potential role of miRNA as biomarkers for diagnosis, histological subtyping and prognosis. In this study, we are exploring the role of miRNA in the histological subtyping of Wilms tumor in the Indian population. MATERIALS AND METHODS: A total of 15 cases of Wilms tumor were evaluated for global miRNA expression analysis by microarray. Total RNA was extracted from fresh frozen tumor and miRNA expression analysis was performed using Agilent platform. Unsupervised clustering was done to analyse the data. RESULTS: Using unpaired student T test, top 10 significantly differentially expressed miRNA were selected which could differentiate among different histological subtypes by unsupervised hierarchical clustering and principal component analysis. The presence of necrosis, heterologous differentiation led to change in miRNA expression profile and led to a distinct cluster formation. CONCLUSIONS: A panel of 5 miRNAs (miR1, 133b, 299-3p, 499a-5p, 491-3p) could differentiate among different histological subtypes of Wilms tumor, thus avoiding an invasive procedure in children, however, further confirmation using real time PCR analysis will be needed.

Circulatory Cytokine Levels as a Predictor of Disease Severity in COVID-19: A Study from Western India.

Inflammatory response in COVID-19 responsible for acute respiratory distress syndrome (ARDS) and multiorgan failure and play a major role in morbidity and mortality of patients. The present study was undertaken to assess serum level of cytokines and its association with other inflammatory markers and disease severity in COVID-19 and hence their prognostic significance. METHODS: This was a retrospective observational study of 175 admitted COVID-19 patients. The patient's clinical data, laboratory investigations, inflammatory markers and serum level of cytokines [interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-10 (IL-10) and tumour necrosis factor α (TNFα)] were extracted from their medical records. All patients were divided into three groups viz. group A had asymptomatic patients, group B had mild to moderate ill patients and group C had severe or critical ill patients. Above parameters were analysed and comparative evaluation with severity of disease was done. RESULTS: & In present study 55% patients were asymptomatic, 24% patients were mild to moderate illness and remaining 21% patients had severe or critical illness. Fever, cough, dyspnoea and co-morbidities including hypertension and diabetes were more common in group C. Absolute lymphocyte count (ALC), lymphocyte monocyte ratio (LMR) showed decreasing trend whereas absolute neutrophil count (ANC), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and eosinophil-lymphocyte (ELR) showed increasing trend with increase in disease severity. Serum IL-6 was found to be significantly higher in group C (64.98±111.18pg/mL) as compared to group B (15.51±20.66pg/mL) and group A (5.04±56.1pg/mL) (P<0.001). Receiver operating characteristic (ROC) curve for IL-6 to differentiate the patients with severe disease from asymptomatic and mild symptomatic disease showed a cut-off of 6.75pg/ml. CONCLUSION: Elevated IL-6 levels lead to adverse clinical events so IL-6 level might serve as a potential prognostic marker for severity of disease in COVID-19. Inhibition of IL-6 might be helpful to prevent serious adverse events in COVID-19 infection.

Obesity, Thyroid and OSA: An Intriguing Triangle.

The complex relationship between BMI, thyroid and its effects on OSA raises a question on how patients with suspected OSA should be evaluated. Some studies have described an association between thyroid disorders and OSA. Whether this is a direct effect of thyroid disorders, or it is indirectly related to BMI values is an important point to ponder. The aim of this study was to estimate the prevalence of thyroid disorders in relation to BMI in newly diagnosed patients with OSA (AHI > 5/h on diagnostic Polysomnography) at sleep lab of our tertiary care centre. In addition, we compared baseline characteristics of OSA patients with thyroid parameters. MATERIAL: In this hospital based observational study, recently diagnosed OSA on the basis of PSG showing AHI > 5/ h according to the AASM 2012 scoring rules and age more than 18 years were recruited from OPD and in-patients of SMS Medical College Jaipur. Patients on previous CPAP treatment, mixed or predominantly central sleep apnea, known diabetics and language barriers or cognitive or psychiatric disorders that made informed consent difficult to obtain were excluded. OBSERVATION: During the study period, 65 patients with treatment naïve OSA and a mean age of 52.28±10.92 year, a mean body mass index (BMI) of 34.73±7.20 kg/m2 underwent thyroid function tests. In the OSA patients, the prevalence of newly diagnosed clinical hypothyroidism was 12.3%. In Mild OSA the mean FT3 (ng/ml), FT4 (ng/dl), TSH (mIU/l) and mean AHI score was 3.10±0.71, 1.37±0.58, 3.64±1.37 and 7.74±3.55 respectively. Similarly, mean FT3 (ng/ml), FT4 (ng/dl), TSH (mIU/l) and mean AHI score were 2.97±0.93, 1.46±0.79, 6.33±8.05 and 17.42±88.90 respectively in moderate OSA and 3.32±0.58, 1.23±0.46, 3.55±1.82 and 45.54±21.38 respectively in severe OSA. There was a statistically significant difference between mild moderate and severe OSA regarding thyroid profile as well as BMI with p of <0.05. CONCLUSION: The prevalence of hypothyroidism was common among patients with OSA and the severity of OSA correlated with thyroid function tests and BMI.

Pazopanib based oral metronomic therapy for platinum resistant/refractory epithelial ovarian cancer: A phase II, open label, randomized, controlled trial.

BACKGROUND: Treatment of patients with platinum resistant/refractory epithelial ovarian cancer (EOC) is an unmet need. We evaluated the role of oral metronomic therapy in this setting. PATIENTS AND METHODS: Between October 2017 and September 2019 seventy five patients with platinum resistant/refractory EOC were enrolled. Patients received oral etoposide (50 mg, day 1 to 14, cyclophosphamide 50 mg, day 1 to 28, every 4 weeks (Arm A, n = 38). Patients in Arm- B (n = 37) received Pazopanib (400 mg once daily) in addition to etoposide and cyclophosphamide. Quality of life (QoL) was evaluated using the EORTC questionnaire. Serum VEGF and PDGF were estimated at baseline, after 3rd and 6th cycle. The primary endpoint was progression free survival (PFS). Secondary endpoints were overall survival (OS), toxicity and QoL. RESULTS: Patients characteristics were well matched. Median PFS was higher in arm B, 5.1 months (95% CI 3.13 to10.33) compared to 3.4 months (95% CI 3.0 to 6.53) in arm A, p = 0.045. Median OS has 'not reached' in Arm B compared to 11.2 months (95% CI, 5.66 - not reached) in arm A, p = 0.032. Therapy was tolerated well; oral mucositis (p = 0.36) and fatigue (p = 0.08) being more in arm B. QoL assessment revealed modest improvement in 'symptom scales' in Arm B. Serum VEGF and PDGF levels decreased with therapy in both arms (Arm A-p < 0.0001, Arm B-p < 0.016). CONCLUSION: Addition of pazopanib to etoposide and cyclophosphamide could be a novel oral combination for metronomic therapy for platinum resistant/refractory EOC. TRIAL REGISTRATION: CTRI/2017/10/010219.

Metabolic changes in triple negative breast cancer-focus on aerobic glycolysis.

Among breast cancer subtypes, the triple negative breast cancer (TNBC) has the worst prognosis. In absence of any permitted targeted therapy, standard chemotherapy is the mainstay for TNBC treatment. Hence, there is a crucial need to identify potential druggable targets in TNBCs for its effective treatment. In recent times, metabolic reprogramming has emerged as cancer cells hallmark, wherein cancer cells display discrete metabolic phenotypes to fuel cell progression and metastasis. Altered glycolysis is one such phenotype, in which even in oxygen abundance majority of cancer cells harvest considerable amount of energy through elevated glycolytic-flux. In the present review, we attempt to summarize the role of key glycolytic enzymes i.e. HK, Hexokinase; PFK, Phosphofructokinase; PKM2, Pyruvate kinase isozyme type 2; and LDH, Lactate dehydrogenase in TNBCs, and possible therapeutic options presently available.

Prognostic and therapeutic relevance of phosphofructokinase platelet-type (PFKP) in breast cancer.

In the present study, we have explored the prognostic value of the Phosphofructokinase Platelet-type (PFKP) expression and its therapeutic relevance in metastatic breast cancer. PFKP immunohistochemistry was performed on Invasive ductal carcinomas (IDCs; n = 87) of breast, and its association with clinicopathological parameters were evaluated. Using online meta-analysis tools, PFKP's prognostic value was investigated in overall breast cancer as well as in triple negative subtype (TNBCs). For in vitro analysis, MDA-MB-231 cells model was used in order to elucidate mechanisms behind PFKP regulated glycolysis and its impact on cancer cell physiology. Therapeutic relevance of PFKP was further evaluated using PFKP siRNA and Quercetin. PFKP protein expression was found to be positively associated with nodal invasion (p = 0.009), receptor (ER & PR) negative status (p = 0.005 & p = 0.028) and reduced overall survival in breast cancer patients (p = 0.014). In MDA-MB-231 cells, quercetin treatment impaired PFKP-LDHA signaling axis thereby inhibiting aerobic glycolysis mediated increased migration of cancer cells. Our present study demonstrates that elevated PFKP levels are associated with basal cells/TNBC subtypes and might serve as prognostic indicator for TNBC patients. Ability of quercetin to inhibit aerobic glycolysis, cell migration and clonogenic potential of malignant breast cancer cells advocates possibility of quercetin in aggressive breast cancer treatment.

Hyperandrogenism, Insulin Resistance, and Acanthosis Nigricans (HAIR-AN) Syndrome Reflects Adipose Tissue Dysfunction ("Adiposopathy" or "Sick Fat") in Asian Indian Girls.

BACKGROUND: Whether HAIR-AN syndrome and polycystic ovarian syndrome (PCOS) are distinct entities or represent a phenotypic spectrum of the same syndrome is still unclear. HAIR-AN syndrome is characterized by high insulin resistance, obesity, and hyperinsulinemia as compared to PCOS and could represent adipose tissue dysfunction as the primary pathophysiologic trigger. This study was undertaken to study the role of adipose tissue dysfunction in HAIR-AN syndrome and PCOS using adipocytokines as surrogate markers of "adiposopathy." MATERIALS AND METHODS: A cross-sectional observational study was conducted at a tertiary care hospital over a period of 1 year. Serum adiponectin, leptin, IL-6, and TNF-α levels were measured in 30 women with HAIR-AN syndrome and in 30 women with PCOS. Correlations between adipocytokines, inflammatory markers, serum testosterone, and serum insulin were determined. Data analysis was performed using the SPSS version 23.0 (IBM SPSS Statistics Inc., Chicago, IL, USA) software program. RESULTS: Women with HAIR-AN syndrome had significantly higher hyperandrogenemia, hyperinsulinemia, and insulin resistance as compared to PCOS women. They also had high leptin levels and lower adiponectin levels (p < 0.001). However, the levels of inflammatory markers (TNF-α and IL-6) were similar in both the groups (p > 0.05). Serum adiponectin showed a negative correlation with HOMA-IR and testosterone levels, while leptin showed a positive correlation with both in HAIR-AN patients while no such correlation was found in the PCOS group. CONCLUSION: The significantly raised adipocytokines in HAIR-AN syndrome patients as compared to PCOS patients indicates the primary role of adipose tissue dysfunction ("adiposopathy") in the pathogenesis of HAIR-AN syndrome while only a minor role, if any, in PCOS. Both these syndromes stand as distinct entities pathogenically with an overlapping phenotype.

Implications of the revised cervical cancer FIGO staging system.

The 2018 revised International Federation of Gynaecology and Obstetrics (FIGO) staging of cervical cancer has brought about a paradigm shift by offering the option of adding imaging and pathology to clinical staging. This makes it applicable to all types of resource situations across geographies with implications for all stakeholders, including gynaecologists, gynaecologic oncologists, radiologists, pathologists and radiation and medical oncologists. The new staging classification has more granularity, with three sub-stages of stage IB and a new category of stage IIIC for all cases with lymph node (LN) involvement. The major limitations of clinical staging were inaccurate assessment of tumour size and inability to assess pelvic and para-aortic LNs with the limited investigations permitted by FIGO to change the stage. This resulted in understaging of stages IB-III, and overstaging of stage IIIB, which has been largely overcome by incorporating imaging findings. Although any imaging modality can be used, magnetic resonance imaging appears to be the best imaging modality for early-stage disease owing to its better soft-tissue resolution. However, the use of contrast-enhanced computed tomography or ultrasonography are also feasible options, depending on the availability and resources. But wherever pathological evaluation is possible, it supersedes clinical and radiological findings.

Feasibility and outcomes of cytoreductive surgery and HIPEC for peritoneal surface malignancies in low- and middle-income countries: a single-center experience of 232 cases.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has recently emerged as a viable management option for peritoneal surface malignancy (PSM). CRS and HIPEC is a complex, multidisciplinary and resource-intensive surgical procedure. It has a steep learning curve and is associated with significant morbidity and mortality. The expertise is mostly limited to few dedicated high-volume centers located in developed countries. We present a single institutional experience of 232 cases of CRS and HIPEC performed at a tertiary care cancer center in a low- and middle-income country (LMIC). METHODS: A multidisciplinary PSM program was initiated in 2015 at a high-volume public-sector tertiary care cancer center in North India catering largely to patients belonging to low- and middle-income groups. Perioperative protocols were developed, and a prospective structured database was created to capture data. All patients undergoing CRS and HIPEC between January 2015 and December 2020 were identified, and the data was retrospectively analyzed for clinical spectrum, surgical details, and perioperative morbidity and mortality. RESULTS: Two hundred and thirty-two patients underwent CRS and HIPEC during the study period. Epithelial ovarian carcinoma (56.5%) was the most common malignancy treated, followed by pseudomyxoma peritonei (18.5%), colorectal carcinoma (13.4%), and malignant mesothelioma (5.6%). Optimal CRS could be achieved in 94.4% of patients. Cisplatin and mitomycin were the most common drugs used for HIPEC. A total of 28.0% of patients had morbidity including deep vein thrombosis, subacute intestinal obstruction, sepsis, burst abdomen, lymphocele, urinoma, acute renal failure, and enterocutaneous fistula. The overall treatment-related mortality was 3.5%. CONCLUSIONS: Results of the current study indicate that it is feasible to establish a successful CRS and HIPEC program for PSM in government-funded hospitals in LMIC facing resource constraints. The most common indication for CRS and HIPEC were carcinoma of the ovary followed by pseudomyxoma peritonei and colorectal carcinoma. Overall morbidity and mortality in the current series are comparable to global standards, reported from high-income countries. A protocol-based multidisciplinary team approach, optimal patient selection, and surgical expertise can help achieve optimal outcomes in government-funded hospitals in LMIC.